Affiliation:
1. From the Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912; the Genetics Institute, Inc., Andover, Massachusetts 01810; and the Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
Abstract
Viral infections induce CD8 T cell expansion and interferon (IFN)-γ production for defense, but the innate cytokines shaping these responses have not been identified. Although interleukin (IL)-12 has the potential to contribute, IL-12–dependent T cell IFN-γ has not been detected during viral infections. Moreover, certain viruses fail to induce IL-12, and elicit high levels of IFN-α/β to negatively regulate it. The endogenous factors promoting virus-induced T cell IFN-γ production were defined in studies evaluating CD8 T cell responses during lymphocytic choriomeningitis virus infections of mice. Two divergent supporting pathways were characterized. Under normal conditions of infections, the CD8 T cell IFN-γ response was dependent on endogenous IFN-α/β effects, but was IL-12 independent. In contrast, in the absence of IFN-α/β functions, an IL-12 response was revealed and substituted an alternative pathway to IFN-γ. IFN-α/β–mediated effects resulted in enhanced, but the alternative pathway also promoted, resistance to infection. These observations define uniquely important IFN-α/β–controlled pathways shaping T cell responses during viral infections, and demonstrate plasticity of immune responses in accessing divergent innate mechanisms to achieve similar ultimate goals.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
256 articles.
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